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SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated innate immunity and lifespan extension.

ABSTRACT: Animals respond to mitochondrial stress with the induction of mitochondrial unfolded protein response (UPR^mt). A cascade of events occur upon UPR^mt activation, ultimately triggering a transcriptional response governed by two transcription factors: DVE-1 and ATFS-1. Here we identify SUMO-specific peptidase ULP-4 as a positive regulator of C. elegans UPR^mt to control SUMOylation status of DVE-1 and ATFS-1. SUMOylation affects these two axes in the transcriptional program of UPR^mt with distinct mechanisms: change of DVE-1 subcellular localization vs. change of ATFS-1 stability and activity. Our findings reveal a post-translational modification that promotes immune response and lifespan extension during mitochondrial stress.

SUBMITTER: Gao K

PROVIDER: S-EPMC6355198 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated innate immunity and lifespan extension.

Gao Kaiyu K Li Yi Y Hu Shumei S Liu Ying Y

eLife 20190115

Animals respond to mitochondrial stress with the induction of mitochondrial unfolded protein response (UPRmt). A cascade of events occur upon UPRmt activation, ultimately triggering a transcriptional response governed by two transcription factors: DVE-1 and ATFS-1. Here we identify SUMO-specific peptidase ULP-4 as a positive regulator of C. elegans UPRmt to control SUMOylation status of DVE-1 and ATFS-1. SUMOylation affects these two axes in the transcript ...[more]

PMID: 30642431

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